Synthesis of β-C-Glycosyl Amino Acids by Ring Opening of Donor-Acceptor Spiro-cyclopropanecarboxylated Sugars

Article abstract of DOI:10.1002/ijch.201500087

The electrophilic ring opening of donor-acceptor spiro-cyclopropanecarboxylated sugars are shown to provide easy access to the stereoselective synthesis of β-C-glycosyl D- and L-alanine derivatives. A possible mechanism is proposed for the ring-opening reaction based on the obtained crystal structure of one of the spiro-cyclic sugar moieties.

Full text of DOI:10.1002/ijch.201500087

Full Paper
DOI: 10.1002/ijch.201500087
Synthesis of b-C-Glycosyl Amino Acids by Ring Opening
of Donor-Acceptor Spiro-cyclopropanecarboxylated Sugars
Bandi Ramakrishna, Chalapala Sudharani, and Perali Ramu Sridhar*[a]
Abstract: The electrophilic ring opening of donor-acceptor
spiro-cyclopropanecarboxylated sugars are shown to provide
easy access to the stereoselective synthesis of b-C-glycosyl
D- and L-alanine derivatives. A possible mechanism is pro-
posed for the ring-opening reaction based on the obtained
crystal structure of one of the spiro-cyclic sugar moieties.
Keywords: amino acids · carboxylation · donor-acceptor systems · glycoproteins · ring opening
1. Introduction
In the last two decades, the crucial role of glycoproteins
in key cellular processes, such as cell recognition, signal-
ing, and immune response, has been understood signifi-
cantly.[1] In these bio-molecules, the sugar unit is attached
to the peptide or protein through either oxygen (as in O-
glycoproteins) or nitrogen (as in N-glycoproteins) atoms.
Biological studies on the evaluation of glycopeptides as
carbohydrate antigens,[2] enzyme inhibitors,[3] and novel
therapeutics[4] has opened a new avenue in drug discov-
ery. In this context, the attachment of the glycan to the
peptide through a CÀC bond has become one of the stra-
tegic approaches in achieving glycopeptide analogues that
are more stable to acidic or enzymatic hydrolysis condi-
tions.[5] This has necessitated the stereoselective synthesis
of various C-glycosyl amino acid precursors. To date, the
majority of the methodologies reported have been on the
synthesis of the a-C-glycosyl analogues of serine, threo-
nine, and asparagine moieties.[5e] Apart from these, a few
methods for the synthesis of C-glycosyl alanine are also
described. The motivation behind the linking of the sugar
moiety and the a-amino acid, D- or L-alanine, through
a CÀC bond is to increase the proximity between the
glycan and the peptide or protein backbone, which could
influence the overall structure of the glycopeptide/pro-
tein.
One of the earlier reports for the synthesis of a-C-gly-
cosylated DL-alanine derivatives involved the generation
of a radical at the anomeric position, followed by its trap-
ping with various dehydroalanine precursors.[6] This pro-
tocol was applied to achieve the synthesis of a-C-glycosyl
DL-alanine derivatives of D-Glc, D-Gal, and D-Lac. Re-
cently, Dondoni et al.[7] cleverly utilized the asymmetric
a-amination reaction catalyzed by D- or L-proline on C-
glycosylalkyl aldehydes to achieve the a- and b-C-(D)-
glycosyl D- and L-amino acids. Apart from these, an
asymmetric Strecker reaction on a-C-(D)-glycosyl acetal-
dehyde,[8] and a cross-metathesis of a gluco-heptenitol de-
rivative with protected allyl or vinyl glycine, followed by
Hg(II) mediated cyclization,[9] are also reported to obtain
a-C-(D)-glycosyl D-alanine derivatives. Consequently, the
Claisen-Ireland rearrangement of 2-O-glycynyl exo-meth-
ylene glycals was shown to provide a-C-glycoamino acid
glycals.[10] On the other hand, a-C-allyl-(D)-glucopyrano-
side was converted to the a-C-(D)-glucosyl D- and L-ala-
nine derivatives in a stereoselective fashion involving
Sharpless asymmetric dihydroxylation as the key step to
incorporate the chirality on the olefin.[11] Very recently,
this protocol was successfully extended to achieve the b-
C-(D)-galactosyl D- and L-alanine derivatives from the
corresponding b-C-allyl-(D)-galactopyranoside, obtained
by a stereoselective Grignard addition to a-(D)-galactosyl
iodide.[12] Another approach for the stereoselective prepa-
ration of 2-deoxy-b-C-(D)-galactosyl D-alanine derivative
was also reported, involving a Wittig reaction of 2-deoxy
(D)-galactosyl phosphoranes with a Garner aldehyde, fol-
lowed by palladium-catalyzed hydrogenation.[13] However,
to the best of our knowledge, the application of donor-ac-
ceptor (DA) cyclopropanes, obtained by the cyclopropa-
nation of exo-methylene glycals, has not been explored
towards the synthesis of C-glycosyl D- and L-alanine de-
rivatives. In continuation of our research in the use of
DA cyclopropanes[14] in the synthesis of various glycoami-
no acids (GAAs),[15] herein we report the synthesis of b-
[a] B. Ramakrishna, C. Sudharani, P. R. Sridhar
School of Chemistry
University of Hyderabad
Gachibowli
Hyderabad-500046
Telangana (India)
e-mail: p_ramu_sridhar@uohyd.ac.in
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/ijch.201500087.
Isr. J. Chem. 0000, 00, 1 – 9
ꢀ 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&1
&
ÞÞ
These are not the final page numbers!

Full Paper
C-(D)-glycosyl D- and L-alanine scaffolds from sugar-de-
rived spiro-cyclopropanecarboxylates.
2. Results and Discussion
Our initial efforts were focused on the preparation of C-
(D)-galactosyl alanine from the D-galactose-derived exo-
glycal 1.[16] Thus, 1 was cyclopropanated with methyldia-
zoacetate in the presence of a catalytic amount of
Rh2(OAc)4 in dichloromethane to afford the spiro-cyclo-
propanecarboxylate 2[17] in 60% yield, as a mixture of
four diastereomers. Interestingly, N-iodosuccinimide
(NIS) mediated solvolytic ring opening of 2 in methanol
provided the iodoketals 3a and 3b, which were separable
as single diastereomers by silica-gel column chromatogra-
phy. Subsequent reaction of iodoketals 3a and 3b with
sodium azide in DMF gave the azido ketals 4a and 4b,[18]
respectively, in good yield (Scheme 1).
Scheme 2. Synthesis of b-C-(D)-galactosyl L- and D-alanine deriva-
tives.
Table 1. Solvolytic ring opening of spiro-cyclopropanecarboxylated
sugar derivatives.
Scheme 1. Synthesis and solvolytic ring opening of D-galactose-
derived spiro-cyclopropanecarboxylate.
Scheme 3. Ring opening of D-fructose-derived spiro-cyclopropane-
carboxylate.
Reaction of the obtained azido ketals 4a and 4b with
Et3SiH, BF3.Et2O in CH2Cl2 provided b-C-(D)-galactosyl
azido esters 5[12] and 6,[12] which were further converted to
the corresponding b-C-(D)-galactosyl alanine derivatives
7 and 8, respectively, using Zn/AcOH-mediated azide re-
duction (Scheme 2).
Encouraged by this result, spiro-cyclopropanecarboxy-
lates 9[17] and 10,[17b] synthesized from the corresponding
exo-glycals, were subjected to a pyranose oxygen-assisted
solvolytic ring-opening reaction in methanol using NIS to
provide the iodoketals 11 and 12, respectively, as a mix-
ture of diastereomers. Substitution of the iodide with
azide led to the formation of azido ketals 13 and 14 in ex-
cellent yield as mixture of diastereomers (Table 1).
To further explore the ring opening of DA spiro-cyclo-
propanecarboxylated sugar derivatives, D-fructose-de-
rived exo-glycal 15[19] was cyclopropanated with methyl-
diazoacetate to provide a mixture of diastereomeric DA
cyclopropanes. Interestingly, purification of this mixture
by column chromatography allowed us to isolate one of
the diastereomers 16, in its pure form, as a solid. Crystal-
lizing 16[20] and subjecting it to single crystal X-ray dif-
fraction studies provided the support to assign the exact
stereochemistry at the newly formed stereocenters. Sub-
jecting 16 to NIS in methanol provided the iodoketal 17
as a single diastereomer, which was further converted to
the azido ketal 18 (Scheme 3). This clearly indicates that
Isr. J. Chem. 0000, 00, 1 – 9
ꢀ 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.ijc.wiley-vch.de
&2
&
ÞÞ
These are not the final page numbers!

Full Paper
the ring-opening reaction that provides the iodoketal as
a single diastereomer is highly stereospecific.
Based on the above observations, a possible mechanism
for the electrophilic ring opening of spiro-cyclopropane-
carboxylated sugar 16 is proposed. Thus, stereospecific
“edge attack” of iodine through the less hindered side of
16 generates an oxocarbenium ion intermediate 19. Trap-
ping of 19 with methanol via a stereoelectronically fa-
vored axial trajectory provides iodoketal 17, as a single
diastereomer, which was converted to the azido ketal 18
through an SN2 reaction (Scheme 4). The stereochemistry
of 18 at the anomeric position was further confirmed by
a 2D NOESY NMR experiment.[21]
Scheme 5. Synthesis of b-C-(D)-glycosyl D- and L-alanine deriva-
tives.
methodology was successfully applied to the preparation
of D-Gal-, D-Glc-, and D-Ara-derived b-C-(D)-glycosyl
alanine derivatives. Further, application of the synthe-
sized GAAs in the preparation of glycopeptide analogues
is in progress.
4. Experimental Section
All the reactions were carried out under nitrogen atmos-
phere and monitored by thin layer chromatography
(TLC) using silica-gel GF254 plates with detection by char-
ring with 5% (v/v) H2SO4 in methanol or by phosphomo-
lybdic acid (PMA) stain or by ultra violet (UV) detection.
All the chemicals were purchased from local suppliers
and Sigma-Aldrich. Solvents used in the reactions were
distilled over dehydrated agents. Silica gel (100–
1
200 mesh) was used for column chromatography. H, 13C,
Scheme 4. Proposed mechanism for the NIS mediated ring open-
ing of DA spiro-cyclopropane carboxylate 16.
DEPT, COSY, and NOESY spectra were recorded on
Bruker 400 MHz and 500 MHz spectrometers in CDCl3
1
and C6D6. H NMR chemical shifts were reported in ppm
Finally, the synthesized azido ketals 13 and 18 were
subjected to BF3.Et2O/Et3SiH to provide C-glycoside de-
rivatives 20 (as a 1:1 mixture of diastereomers) and 23
(as a single diastereomer), which were further converted
to b-C-(D)-glucosyl L-alanine derivative 21[7] and b-C-
(D)-glucosyl D-alanine derivative 22,[7] and b-C-(D)-ara-
binosyl L-alanine derivative 24, respectively (Scheme 5).
(d) with TMS as internal standard (d 0.00) and 13C NMR
were reported in chemical shifts with solvent reference
(CDCl3, d 77.00). High resolution mass spectra (HRMS)
were obtained in the ESI mode using a Bruker maXis
QTOF spectrometer.
(3R,5R,6S,7S,8R)-Methyl 6,7,8-tris(benzyloxy)-5-(ben-
zyloxymethyl)-4-oxaspiro[2.5]octane-1-carboxylate (2): To
a stirred suspension of exo-glycal 1 (4.4 g, 8.20 mmol) and
Rh2(OAc)4 (72 mg, 0.16 mmol) in anhydrous CH2Cl2
(30 mL), over a period of 1 h, a solution of methyl diazo-
acetate (2.28 mL, 24.6 mmol) in CH2Cl2 (70 mL) was
added dropwise. After completion of the reaction, the re-
action mixture was concentrated in vacuo and the ob-
tained crude product was purified by silica-gel column
chromatography, which gave the desired spiro-cyclopro-
panecarboxylate 2 (2.9 g, 60%) as a mixture of four dia-
stereomers. IR (neat): nmax 3063, 3030, 2947, 2871, 1736,
1495, 1452, 1364 cmÀ1. HRMS calcd. for C38H40O7 +Na
631.2672, found 631.2670.
3. Conclusion
In conclusion, a general methodology for the stereoselec-
tive synthesis of b-C-(D)-glycosyl D- and L-alanine deriv-
atives from donor-acceptor spiro-cyclopropanecarboxylat-
ed sugars was revealed. The approach of the O-nucleo-
philic, MeOH, via the axial trajectory due to the anome-
ric effect was utilized as a tool to achieve the formation
of a b-C-glycosidic bond in the electrophilic ring opening
of spiro-cyclopropanecarboxylated donors. The developed
Isr. J. Chem. 0000, 00, 1 – 9
ꢀ 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.ijc.wiley-vch.de
&3
&
ÞÞ
These are not the final page numbers!

Full Paper
(S)-Methyl 2-iodo-3-((2S,3R,4S,5S,6R)-3,4,5-tris(benzy-
loxy)-6-((benzyloxy)methyl)-2-methoxytetrahydro-2H-
pyran-2-yl)propanoate (3a) and (R)-Methyl 2-iodo-3-
((2S,3R,4S,5S,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)-
methyl)-2-methoxytetrahydro-2H-pyran-2-yl)propanoate
(3b): To a stirred solution of D-galactose-derived spiro-
cyclopropane carboxylate 2 (3.3 g, 5.42 mmol) in metha-
nol (20 mL) at 08C under nitrogen, N-iodosuccinimide
(NIS) (1.45 g, 6.5 mmol) was added. The reaction mixture
was stirred for 48 h at room temperature. After complete
conversion of the starting material, confirmed by TLC,
the reaction was quenched with saturated sodium thiosul-
fate. Methanol was evaporated under reduced pressure
and the obtained residue was extracted with dichlorome-
thane (3ꢀ100 mL). Finally, the combined organic layer
was washed with water and brine solution, and concen-
trated on a rotary evaporator. The obtained crude prod-
uct was purified by silica-gel column chromatography to
afford the ring-opened iodo-carboxylates 3a and 3b (2.9 g,
70%) as a colorless gum. (3a): IR (neat): nmax 3062, 3035,
tained residue was extracted with dichloromethane (3ꢀ
50 mL). The combined organic layer was washed with
water and brine, dried over anhydrous MgSO4 and con-
centrated. The obtained crude product was purified by
silica-gel column chromatography to provide the corre-
sponding azido carboxylate 4a (0.98 g, 85%) as a colorless
liquid. IR (neat): nmax 3084, 3068, 3024, 2915, 2871, 2104,
1
1742, 1495, 1463, 1358 cmÀ1. H NMR (500 MHz, CDCl3):
d 7.28–7.42 (m, 20H), 5.02 (d, 1H, J=10.5 Hz), 5. 01 (d,
1H, J=12.0 Hz), 4.74–4.80 (m, 3H), 4.61 (d, 1H, J=
11.5 Hz), 4.53 (d, 1H, J=11.5 Hz), 4.46 (d, 1H, J=
11.5 Hz), 4.09 (bs, 2H), 4.07 (bs, 1H), 3.94 (dd, 1H, J=
4.0 Hz, J=7.5 Hz), 3.81 (t, 1H, J=6.5 Hz), 3.70 (t, 1H,
J=4.5 Hz), 3.65 (s, 3H), 3.61 (dd, 1H, J=5.5 Hz, J=
9.0 Hz), 3.28 (s, 3H), 2.43 (dd, 1H, J=4.5 Hz, J=
15.0 Hz), 2.24 (dd, 1H, J=8.0 Hz, J=15.0 Hz). 13C NMR
(125 MHz, CDCl3): d 170.6, 139.0, 138.4, 138.2, 138.0,
128.4 128.4, 128.3, 128.2, 127.7, 127.6, 127.6, 127.5, 127.4,
127.3, 100.7, 80.8, 77.2, 75.6, 74.6, 74.4, 73.5, 72.4, 70.8,
68.8, 58.6, 52.5, 48.1, 33.4. HRMS calcd. for C39H43N3O8 +
Na 704.2948, found 704.2948.
1
2920, 2865, 1747, 1632, 1500, 1451, 1363 cmÀ1. H NMR
(500 MHz, CDCl3): d 7.27–7.41 (m, 20H), 5.03 (d, 1H, J=
12.0 Hz), 4.97 (d, 1H, J=11.0 Hz), 4.74–4.80 (m, 3H),
4.58 (d, 1H, J=11.5 Hz), 4.48 (d, 1H, J=11.5 Hz), 4.41
(d, 1H, J=12.0 Hz), 4.00–4.09 (m, 4H), 3.68 (dt, 1H, J=
2.0 Hz, J=7.0 Hz), 3.50–3.54 (m, 4H), 3.40 (dd, 1H, J=
5.5 Hz, J=9.0 Hz), 3.26 (s, 3H), 2.97 (dd, 1H, J=12.5 Hz,
J=14.0 Hz), 2.39 (dd, 1H, J=2.5 Hz, J=14.5 Hz). 13C
NMR (125 MHz, CDCl3): d 171.9, 139.1, 138.3, 137.7,
128.9, 128.7, 128.4, 128.2, 128.0, 127.8, 127.7, 127.6, 127.5,
127.2, 127.1, 102.0, 80.6, 75.5, 75.0, 74.6, 74.3, 73.5, 72.4,
70.4, 68.3, 52.3, 48.3, 38.6, 13.9. HRMS (ESI) calcd. for
C39H43IO8 +Na 789.1900, found 789.1902. (3b): IR (neat):
nmax 3059, 3032, 2924, 2859, 1742, 1629, 1495, 1455, 1360,
1252, 1215, 1060 cmÀ1. 1H NMR (400 MHz, CDCl3): d
7.27–7.37 (m, 20H), 5.01 (d, 1H, J=11.2 Hz), 4.96 (d, 1H,
J=10.8 Hz), 4.78 (d, 1H, J=10.8 Hz), 4.75 (d, 1H, J=
5.2 Hz), 4.72 (d, 1H, J=11.6 Hz), 4.54 (d, 1H, J=3.6 Hz),
4.52 (d, 1H, J=4.4 Hz), 4.49 (d, 1H, J=10.0 Hz), 4.47 (d,
1H, J=19.2 Hz), 3.92–4.01 (m, 3H), 3.72 (t, 1H, J=
6.8 Hz), 3.59 (dd, 1H, J=7.2 Hz, J=7.6 Hz), 3.50 (dd, 1H,
J=5.6 Hz, J=9.2 Hz), 3.37 (s, 3H), 3.21 (s, 3H), 2.83 (dd,
1H, J=11.6 Hz, J=15.2 Hz), 2.42 (dd, 1H, J=3.6 Hz, J=
15.2 Hz). 13C NMR (100 MHz, CDCl3): d 171.9, 138.9,
138.4, 138.2, 137.9, 128.6, 128.4, 128.3, 128.1, 127.8, 127.8,
127.7, 127.6, 127.5, 127.4, 100.8, 80.8, 78.9, 77.2, 75.7, 74.7,
73.6, 72.5, 70.7, 68.5, 52.4, 48.4, 41.1, 14.8. HRMS calcd.
for C39H43IO8 +Na 789.1900, found 789.1904.
(S)-Methyl 2-azido-3-((2S,3R,4S,5S,6R)-3,4,5-tris(benzyl-
oxy)-6-((benzyloxy)methyl)-2-methoxytetrahydro-2H-
pyran-2-yl)propanoate (4b): Compound 4b was synthe-
sized from 3b (1.2 g, 1.56 mmol) according to the proce-
dure described for compound 4a. Yield (0.89 g, 84 %).
[a]2D5 +11.2 (c 0.86, CHCl3); IR (neat): nmax 3089, 3058,
1
3029, 2921, 2847, 2105, 1745, 1506, 1452, 1360 cmÀ1. H
NMR (500 MHz, CDCl3): d 7.28–7.40 (m 20H), 5.03 (d,
1H, J=9.5 Hz), 5.00 (d, 1H, J=9.5 Hz), 4.80 (d, 1H, J=
11.5 Hz), 4.79 (d, 1H, J=16.5 Hz), 4.75 (d, 1H, J=
11.5 Hz), 4.56 (d, 1H, 11.5 Hz), 4.50 (d, 1H, J=12.0 Hz),
4.44 (d, 1H, J=12.0 Hz), 4.17 (d, 1H, J=10.0 Hz), 4.08
(dd, 1H, J=2.5 Hz, J=9.5 Hz), 4.01 (d, 1H, J=1.0 Hz ),
3.73–3.77 (m, 2H), 3.59 (s, 3H), 3.56 (dd, 1H, J=8.0 Hz,
J=9.5 Hz), 3.48 (dd, 1H, J=5.5 Hz, J=9.0 Hz), 3.25 (s,
3H), 2.38 (dd, 1H, J=7.0 Hz, J=14.5 Hz), 2.03 (dd, 1H,
J=6.5 Hz, J=14.5 Hz). 13C NMR (100 MHz, CDCl3): d
170.6, 139.0, 138.3, 138.0, 137.8, 128.6, 128.4, 128.3, 128.1,
127.7, 127.7, 127.6, 127.5, 127.4, 127.3, 100.1, 80.9, 77.2,
76.3, 75.2, 74.5, 74.4, 73.5, 72.4, 70.5, 68.5, 58.2, 52.3, 48.0,
32.3. HRMS calcd. for C39H43N3O8 +Na 704.2948, found
704.2948.
(R)-Methyl 2-azido-3-((2S,3S,4R,5S,6R)-3,4,5-tris(ben-
zyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-yl)-
propanoate (5): To a solution of azido carboxylate 4a
(700 mg, 1.02 mmol) in dry dichloromethane (10 mL),
freshly distilled triethyl silane (3.25 mL, 20.55 mmol) was
added and the reaction mixture was cooled to À788C,
then freshly distilled BF3.Et2O (1.29 mL, 10.30 mmol) was
added dropwise, over a period of 10 minutes, via syringe.
The reaction was warmed to À508C, and allowed to stir
for an additional 4 h. After completion of the reaction,
checked by TLC, the reaction mixture was quenched by
the addition of saturated aqueous NaHCO3 solution
(10 mL). The mixture was taken into a separating funnel
(R)-Methyl 2-azido-3-((2S,3R,4S,5S,6R)-3,4,5-tris(ben-
zyloxy)-6-((benzyloxy)methyl)-2-methoxytetrahydro-2H-
pyran-2-yl)propanoate (4a): To a stirred solution of 3a
(1.3 g, 1.69 mmol) in N,N-dimethylformamide (10 mL),
sodium azide (0.505 g, 8.47 mmol) was added and the re-
action mixture was stirred at room temperature for 4 h.
After completion of the reaction, monitored by TLC, the
solvent was removed under reduced pressure and the ob-
Isr. J. Chem. 0000, 00, 1 – 9
ꢀ 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.ijc.wiley-vch.de
&4
&
ÞÞ
These are not the final page numbers!

Full Paper
and the aqueous layer was extracted with dichlorome-
thane (3ꢀ50 mL). The combined organic layer was
washed with water and brine solution, and dried over an-
hydrous Na2SO4. Removal of the solvent under reduced
pressure, and purification of the crude product by silica-
20H), 4.95 (d, 1H, J=4.0 Hz), 4.92 (d, 1H, J=5.0 Hz),
4.74 (d, 1H, J=11.5 Hz), 4.66 (d, 1H, J=11.5 Hz), 4.63
(d, 1H, J=2.0 Hz), 4.61 (d, 1H, J=3.0 Hz), 4.43 (q, 2H,
J=11.5 Hz), 3.98 (d, 1H, J=3.0 Hz), 3.69 (t, 1H, J=
3.5 Hz), 3.67 (s, 3H), 3.61 (dd, 1H, J=2.5 Hz, J=9.0 Hz),
3.52–3.55 (m, 3H), 3.46–3.50 (m, 1H), 1.98–2.07 (m, 1H),
1.91–1.97 (m, 2H), 1.70 (bs, 2H). 13C NMR (100 MHz,
CDCl3): d 176.6, 138.6, 138.2, 137.9, 128.4, 128.3, 128.2,
128.2, 128.0, 127.9, 127.7, 127.6, 127.5, 84.7, 78.6, 77.2,
76.1, 75.3, 74.5, 73.7, 73.4, 72.3, 68.9, 51.9, 51.2, 36.3.
HRMS calcd. for C38H43NO7 +H 626.3118, found
626.3117.
(S)-Methyl 2-amino-3-((2S,3S,4R,5S,6R)-3,4,5-tris(ben-
zyloxy)-6-(benzyloxymethyl) tetrahydro-2H-pyran-2-yl)-
propanoate (8): Compound 8 was synthesized using azido
carboxylate 6 (25 mg, 0.03 mmol), Zn (2.5 mg, 0.03 mmol)
and acetic acid/tetrahydrofuran (1:1) (2 mL) following
the procedure described for compound 7. Compound 8
(15.0 mg, 62%) was obtained as a colorless gum. [a]D25
+0.3 (c 0.7, CHCl3); IR (neat): nmax 2958, 2926, 2854,
1742, 1452, 1369 cmÀ1. 1H NMR (500 MHz, CDCl3): d
7.27–7.36 (m, 20H), 4.95 (d, 1H, J=5.0 Hz), 4.92 (d, 1H,
J=5.5 Hz), 4.74 (d, 1H, J=11.5 Hz), 4.67 (d, 1H, J=
7.0 Hz), 4.64 (d, 1H, J=6.5 Hz), 4.60 (d, 1H, J=7.50 Hz),
4.45 (d, 1H, J=11.5 Hz), 4.40 (d, 1H, J=11.5 Hz), 3.97
(d, 1H, J=2.5 Hz), 3.69 (d, 1H, J=6.5 Hz), 3.68 (d, 1H,
J=5.0 Hz), 3.66 (s, 3H), 3.58 (dd, 1H, J=2.5 Hz, J=
9.0 Hz), 3.50–3.55 (m, 3H), 3.40 (dt, 1H, J=2.0 Hz, J=
9.0 Hz, J=18.5 Hz), 2.29 (ddd, 1H, J=2.0 Hz, J=5.5 Hz,
J=14.0 Hz), 2.02 (bs, 2H), 1.78 (ddd, 1H, J=6.5 Hz, J=
9.5 Hz, J=15.5 Hz). 13C NMR (100 MHz, CDCl3): d
175.5, 138.7, 138.2, 137.8, 128.4, 128.3, 128.2, 128.1, 127.9,
127.8, 127.7, 127.6, 127.5, 84.6, 78.7, 77.5, 76.8, 75.4, 74.5,
73.7, 73.5, 72.2, 68.8, 52.4, 51.9. 37.0. HRMS calcd. for
C38H43NO7 +H 626.3118, found 626.3116.
gel column chromatography, afforded compound
5
(540 mg, 80%) as a colorless liquid. [a]2D5 À14.8 (c 0.5,
CHCl3); IR (neat): nmax 3085, 3066, 3030, 2923, 2854,
2111, 1743, 1496, 1454, 1436, 1363 cmÀ1. 1H NMR
(400 MHz, CDCl3): d 7.28–7.40 (m, 20H), 4.99 (d, 1H, J=
4.8 Hz), 4.96 (d, 1H, J=5.2 Hz), 4.78 (d, 1H, J=12.0 Hz),
4.69 (dd, 2H, J=6.4 Hz, J=13.6 Hz), 4.65 (d, 1H, J=
2.8 Hz), 4.47 (q, 2H, J=12.0 Hz), 4.17 (dd, 1H, J=3.2 Hz,
J=11.2 Hz), 4.05 (d, 1H, J=2.4 Hz), 3.76 (s, 3H), 3.70 (d,
1H, J=9.2 Hz), 3.65 (dd, 1H, J=2.4 Hz, J=9.2 Hz), 3.55–
3.59 (m, 3H), 3.43–3.48 (m, 1H), 2.16–2.23 (m, 1H), 1.93–
2.00 (m, 1H). 13C NMR (100 MHz, CDCl3): d 171.9, 138.6,
138.2, 138.2, 137.9, 128.4, 128.4, 128.4, 128.3, 128.2, 128.0,
127.9, 127.8, 127.7, 127.6, 127.6, 84.7, 78.5, 76.9, 75.3, 74.7,
73.7, 73.5, 72.3, 68.7, 58.6, 52.5, 33.9. HRMS calcd. for
C38H41N3O7 +Na 674.2842, found 674.2843.
(S)-Methyl 2-azido-3-((2S,3S,4R,5S,6R)-3,4,5-tris(benzyl-
oxy)-6-((benzyloxy)methyl)
tetrahydro-2H-pyran-2-yl)-
propanoate (6): Compound 6 was synthesized from 4b
(600 mg, 0.88 mmol) following the procedure described
for compound 5. Yield (480 mg, 82%). [a]2D5 À15.2 (c 0.5,
CHCl3); IR (neat): nmax 3066, 3030, 2923, 2853, 2106,
1
1743, 1541, 1496, 1454, 1362 cmÀ1. H NMR (400 MHz,
CDCl3): d 7.28–7.37 (m, 20H), 4.96 (dd, 2H, J=9.6 Hz,
J=11.2 Hz), 4.75 (d, 1H, J=11.6 Hz), 4.61–4.68 (m, 3H),
4.44 (q, 2H, J=12.0 Hz), 4.10 (dd, 1H, J=5.2 Hz, J=
7.6 Hz), 4.01 (d, 1H, J=2.8 Hz), 3.75 (dd, 1H, J=7.2 Hz,
J=13.2 Hz), 3.71 (s, 3H), 3.60 (dd, 1H, J=2.8 Hz, J=
9.2 Hz), 3.51–3.56 (m, 3H), 3.36–3.42 (m, 1H), 2.34 (ddd,
1H, J=2.8 Hz, J=7.2 Hz, J=14.0 Hz), 1.93–2.00 (m, 1H).
13C NMR (100 MHz, CDCl3): d 170.7, 138.7, 138.2, 138.1,
137.9, 128.4, 128.4, 128.2, 128.1, 128.0, 127.9, 127.8, 127.7,
127.6, 84.7, 78.1, 76.8, 75.7, 75.3, 74.6, 73.6, 73.5, 72.2,
68.5, 59.0, 52.4, 33.8. HRMS calcd. for C38H41N3O7 +Na
674.2842, found 674.2845.
Methyl
2-iodo-3-((2S,3R,4S,5R,6R)-3,4,5-tris(benzyl-
tetrahydro-2H-
oxy)-6-((benzyloxy)methyl)-2-methoxy
pyran-2-yl)propanoate (11): Compound 11 was synthe-
sized from 9 (2.0 g, 3.28 mmol) by following the proce-
dure described for compound 3a. Compound 11 (1.8 g,
72%) was obtained as an inseparable diastereomeric mix-
ture in 1:1 ratio. IR (neat): nmax 3062, 3035, 2920, 2865,
1747, 1632, 1500, 1451, 1363 cmÀ1. HRMS calcd. for
C39H43IO8 +Na 789.1900, found 789.1902.
(R)-Methyl 2-amino-3-((2S,3S,4R,5S,6R)-3,4,5-tris(ben-
zyloxy)-6-(benzyloxymethyl) tetrahydro-2H-pyran-2-yl)-
propanoate (7): To a stirred solution of azide 5 (30 mg,
0.04 mmol) in AcOH/THF (3 mL, 1:1), Zn dust (3.0 mg,
0.04 mmol) was added, and the reaction mixture was
stirred for 12 h at room temperature. After completion of
the reaction, Zn was removed by filtration, then the sol-
vent was removed under vacuum. The obtained residue
was dissolved in ethyl acetate (20 mL). The solution was
washed with saturated NaHCO3 solution, water and
brine, dried over anhydrous Na2SO4, and concentrated.
Purification of the crude product by silica-gel column
chromatography gave the b-C-(D)-galactosyl L-alanine
derivative 7 (18 mg, 64%) as a colorless gum.[a]2D5 À3.2 (c
0.6, CHCl3); IR (neat): nmax 2920, 2854, 1742, 1463,
Methyl
2-azido-3-((2S,3R,4S,5R,6R)-3,4,5-tris(benzyl-
tetrahydro-2H-
oxy)-6-(benzyloxymethyl)-2-methoxy
pyran-2-yl)propanoate (13): Compound 13 was synthe-
sized from 11 (1.0 g, 1.39 mmol) by following the proce-
dure described for compound 4a. Compound 13 (0.82 g,
92%) was obtained as an inseparable diastereomeric mix-
ture in 1:1 ratio. IR (neat): nmax 3095, 3063, 3024, 2926,
2854, 2109, 1747, 1501, 1457, 1364 cmÀ1. HRMS calcd. for
C39H43N3O8 +Na 704.2948, found 704.2951.
Methyl
2-azido-3-((2S,3S,4R,5R,6R)-3,4,5-tris(benzyl-
oxy)-6-(benzyloxymethyl)tetrahydro-2H-pyran-2-yl)pro-
panoate (20): Compound 20 was synthesized from 13
1
1364 cmÀ1. H NMR (500 MHz, CDCl3): d 7.26–7.34 (m,
Isr. J. Chem. 0000, 00, 1 – 9
ꢀ 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.ijc.wiley-vch.de
&5
&
ÞÞ
These are not the final page numbers!

Full Paper
(300 mg, 0.44 mmol) by following the procedure de-
scribed for compound 5. Compound 20 (225 mg, 78%)
was obtained as an inseparable diastereomeric mixture in
1:1 ratio. IR (neat): nmax 3095, 3063, 3024, 2926, 2854,
2109, 1747, 1501, 1457, 1364 cmÀ1. HRMS calcd. for
C38H41N3O7 +Na 674.2842, found 674.2844.
data is completely in agreement with the reported
values).
Methyl 3-((2R,3S,4R)-3,4-bis(benzyloxy)-2-methoxyte-
trahydro-2H-pyran-2-yl)-2-iodopropanoate (12): Com-
pound 12 was synthesized from 10 (870 mg, 2.27 mmol)
by following the procedure described for compound 3a.
Compound 12 (0.9 g, 73 %) was obtained as an insepara-
ble diastereomeric mixture. IR (neat): nmax 3063, 3030,
2953, 2882, 1736, 1495, 1452, 1435, 1364 cmÀ1. HRMS
calcd. for C24H29IO6 +Na 563.0907, found 563.0909.
Methyl 2-azido-3-((2R,3S,4R)-3,4-bis(benzyloxy)-2-me-
thoxytetrahydro-2H-pyran-2-yl)propanoate (14): Com-
pound 14 was synthesized from 12 (830 mg, 1.53 mmol)
by following the procedure described for compound 4a.
Compound 14 (489 mg, 70%) was obtained as an insepa-
rable diastereomeric mixture in 4 :1 ratio. IR (neat): nmax
3090, 3068, 3035, 2926, 2865, 1720, 1501, 1457 cmÀ1. Data
for the major isomer: 1H NMR (500 MHz, CDCl3): d
7.28–7.39 (m, 10 H), 5.06 (d, 1H, J=11.5 Hz), 4.82 (d, 1H,
J=11.5 Hz), 4.67 (q, 2H, J=11.5 Hz), 4.01–4.07 (m, 1H),
3.76–3.79 (m, 1H), 3.74 (s, 3H), 3.58–3.64 (m, 2H), 3.49–
3.54 (m, 1H), 3.24 (s, 3H), 2.33 (dd, 1H, J=6.5 Hz, J=
14.5 Hz), 2.05–2.13 (m, 2H), 1.66 (ddd, 1H, J=5.5 Hz, J=
13.0 Hz, J=24.5 Hz). 13C NMR (100 MHz, CDCl3): d
170.6, 138.4, 138.2, 128.4, 128.3, 128.3, 128.2, 127.6, 127.5,
100.3, 80.7, 76.6, 75.0, 71.6, 59.0, 58.3, 52.4, 47.5, 32.6,
31.4. HRMS calcd. for C24H29N3O6 +Na 478.1954, found
478.1954.
(S)-Methyl
2-((tert-butoxycarbonyl)amino)-3-
((2S,3S,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)me-
thyl)tetrahydro-2H-pyran-2-yl)propanoate (21)[7] and (R)-
methyl 2-(tert-butoxycarbonylamino)-3-((2S,3S,4R,5R,6R)-
3,4,5-tris(benzyloxy)-6-(benzyloxymethyl) tetrahydro-2H-
pyran-2-yl)propanoate (22):[7] Triphenyl phosphine
(16 mg, 0.06 mmol) was added to a solution of azide 20
(40 mg, 0.06 mmol) in dry THF (3 mL) under nitrogen at-
mosphere and the solution was stirred for 8 h. After com-
plete formation of iminophosphorane was confirmed by
TLC, water was added and the solution was refluxed for
6 h. The reaction mixture was washed with brine solution
and extracted with chloroform. The organic extract was
dried over anhydrous Na2SO4 and evaporated. The ob-
tained residue was co-evaporated with toluene twice in
vacuo and dried. The residue was dissolved in CH2Cl2
(3 mL) and Et3N (18.7 mL), Boc2O (65.17 mL, 0.27 mmol)
was added successively and the reaction mixture was
stirred overnight. After complete conversion of the reac-
tion mixture, checked by TLC, the solvent was removed
in vacuo, diluted with water, extracted with EtOAc
(25 mLꢀ3), washed with water (30 mL), and brine
(30 mL), and dried over anhydrous Na2SO4, concentrated.
Purification of the crude product by column chromatogra-
phy afforded the b-C-(D)-glucosyl L-alanine derivative 21
and b-C-(D)-glucosyl D-alanine derivative 22 as single
diastereomers (1:1 ratio) in 77% overall yield. 21: IR
(neat): nmax 3391, 3084, 3057, 3030, 2920, 2854, 1797, 1720,
(1’R,2’R,3aR,7S,7aR)-Methyl 7-((tert-butyldimethylsilyl)-
oxy)-2,2-dimethyltetrahydrospiro[[1,3]
dioxolo[4,5-
c]pyran-6,1’-cyclopropane]-2’-carboxylate (16): Com-
pound 16 was synthesized from 15 (1.0 g, 3.33 mmol) by
following the procedure described for compound 2. Com-
pound 16 (150 mg, 12%) was obtained as a colorless
solid. Overall yield of the 4 diastereomers (0.73 g, 58%).
1
1495, 1452, 1364 cmÀ1. H NMR (400 MHz, C6D6): d 7.05–
1
7.38 (m, 20H), 5.9 (d, 1H, J=8.8 Hz), 4.87–4.93 (m, 1H),
4.82 (d, 1H, J=11.2 Hz), 4.79 (d, 1H, J=11.2 Hz), 4.77
(d, 1H, J=11.2 Hz), 4.75 (d, 1H, J=11.2 Hz), 4.56 (d, 1H,
J=11.6 Hz), 4.55 (d, 1H, J=12.4 Hz), 4.42 (d, 1H, J=
12.4 Hz), 4.37 (d, 1H, J=11.2 Hz), 3.53–3.68 (m, 4H),
3.43 (t, 1H, J=9.2 Hz), 3.29–3.36 (m, 1H), 3.26 (s, 3H),
3.10 (t, 1H, J=9.2 Hz), 2.23 (m, 1H), 1.80 (m, 1H) ppm.
HRMS calcd. for C43H51NO9 +Na 748.3462, found
748.3460. (The spectral data is completely in agreement
with the reported values). 22: IR (neat): nmax 3389, 3079,
Data for compound 16: [a]2D5 +1.8 (c 1, CHCl3); H NMR
(400 MHz, CDCl3): d 4.35 (ddd, 1H, J=6.0 Hz, J=8.4 Hz,
J=14.4 Hz), 4.15 (d, 1H, J=2.4 Hz), 4.10 ( dd, 1H, J=
2.4 Hz, J=5.6 Hz), 3.90 (dd, 1H, J=6.4 Hz, J=11.6 Hz),
3.67 (s, 3H), 3.43 (dd, 1H, J=8.4 Hz, J=11.2 Hz), 1.95
(dd, 1H, J=7.2 Hz, J=8.8 Hz), 1.46 (s, 3H), 1.35–1.42 (m,
2H), 1.32 ( s, 3H), 0.90 (s, 9H), 0.13 (s, 3H), 0.12 (s, 3H).
13C NMR (100 MHz, CDCl3): d 172.1, 109.6, 75.7, 69.1,
66.4, 65.7, 65.5, 51.7, 27.5, 26.8, 26.0, 25.7, 19.0, 18.0, À4.4,
À4.8, À5.1. HRMS calcd. for C18H32O6 +Na 395.1866,
found 395.1866.
1
3051, 3028, 2923, 2857, 1792, 1715, 1488, 1454 cmÀ1. H
NMR (400 MHz, C6D6): d 7.06–7.30 (m, 20H), 5.60 (d,
1H, J=6.8 Hz), 4.82 (d, 1H, J=11.2 Hz), 4.80 (d, 1H, J=
6.0 Hz), 4.75 (d, 1H, J=14.8 Hz), 4.69 (d, 1H, J=
11.6 Hz), 4.67 (d, 1H, J=4.4 Hz), 4.59 (d, 1H, J=
11.6 Hz), 4.42 (d, 1H, J=11.6 Hz), 4.39 (d, 1H, J=
12.4 Hz), 4.28 (d, 1H, J=12.0 Hz), 3.71 (t, 1H, J=
9.2 Hz), 3.56–3.60 (m, 2H), 3.52 (t, 1H, J=8.8 Hz), 3.38–
3.41 (m, 1H), 3.36 (s, 3H), 3.10 (t, 1H, J=8.8 Hz), 2.52
(m, 1H), 1.90 (m, 1H), 1.42 (s, 9H). HRMS calcd. for
C43H51NO9 +Na 748.3462, found 748.3460. (The spectral
(R)-Methyl 3-((3aR,6S,7S,7aR)-7-(tert-butyldimethylsi-
lyloxy)-6-methoxy-2,2-dimethyltetra-hydro-3aH-[1,3]diox-
olo[4,5-c]pyran-6-yl)-2-iodopropanoate (17): Compound
17 was synthesized from 16 (120 mg, 0.32 mmol) by fol-
lowing the procedure described for compound 3a. Com-
pound 17 (160 mg, 94%) was obtained as a colorless
liquid. IR (neat): nmax 2931, 2865, 1742, 1457, 1435,
1
1364 cmÀ1. H NMR (400 MHz, CDCl3): d 4.49 (dd, 1H,
J=3.6 Hz, J=10.8 Hz), 4.15–4.18 (m, 1H), 4.06 (dd, 1H,
J=6.0 Hz, J=6.8 Hz), 3.80–3.86 (m, 2H), 3.71 (s, 3H),
Isr. J. Chem. 0000, 00, 1 – 9
ꢀ 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.ijc.wiley-vch.de
&6
&
ÞÞ
These are not the final page numbers!

Full Paper
3.59 (d, 1H, J=7.2 Hz), 3.27 (s, 3H), 2.82 (dd, 1H, J=
10.8 Hz, J=15.2 Hz), 2.52 (dd, 1H, J=4.0 Hz, J=
15.6 Hz), 1.49 (s, 3H), 1.31 (s, 3H), 0.90 (s, 9H), 0.16 (s,
6H). 13C NMR (100 MHz, CDCl3): d 172.1, 108.6, 100.6,
75.8, 73.3, 60.4, 52.7, 49.8, 40.9, 28.12, 26.2, 25.9, 18.2,
13.8, À3.8, À5.1. HRMS calcd. for C19H35IO7Si+Na
553.1094, found 553.1095.
CDCl3): d 5.30 (d, 1H, J=6.8 Hz), 4.38 (q, 1H, J=
5.6 Hz), 4.12 (dd, 1H, J=2.0 Hz, J=5.6 Hz), 4.09 (d, 1H,
J=13.6 Hz), 3.88 (t, 1H, J=6.0 Hz), 3.68 (s, 3H), 3.59
(dd, 1H, J=2.0 Hz, J=13.2 Hz), 3.36 (dd, 1H, J=6.8 Hz,
J=9.6 Hz), 3.06 (t, 1H, J=9.2 Hz), 2.34 (dd, 1H, J=
4.8 Hz, J=14.4 Hz), 1.71–1.78 (m, 1H), 1.50 (s, 3H), 1.41
(s, 9H), 1.33 (s, 3H), 0.86 (s, 9H), 0.12 (s, 3H), 0.06 (s,
3H). 13C NMR (100 MHz, CDCl3): d 173.0, 154.9, 109.1,
79.8, 79.6, 76.1, 74.1, 74.0, 66.5, 52.2, 51.2, 34.2, 28.3, 28.1,
26.3, 25.8, 17.9, À3.9, À5.0. HRMS calcd. for
C23H43NO8Si+Na, 512.2656 found 512.2660.
(S)-Methyl 2-azido-3-((3aR,6S,7S,7aR)-7-(tert-butyldi-
methylsilyloxy)-6-methoxy-2,2-dimethyltetrahydro-3aH-
[1,3]dioxolo[4,5-c]pyran-6-yl)propanoate (18): Compound
18 was synthesized from 17 (150 mg, 0.28 mmol) by fol-
lowing the procedure described for compound 4a. Com-
pound 18 (110 mg, 88%) was obtained as a colorless
liquid. IR (neat): nmax 2988, 2958, 2926, 2860, 2098, 1747,
1457, 1430, 1375 cmÀ1. 1H NMR (400 MHz, CDCl3): d
4.18–4.21 (m, 1H), 4.10 (t, 1H, J=7.2 Hz), 3.96 (q, 1H,
J=6.8 Hz), 3.88 (dd, 1H, J=0.8 Hz, J=13.2 Hz), 3.81 (d,
1H, J=7.2 Hz), 3.78 (s, 3H), 3.75 (dd, 1H, J=3.2 Hz, J=
8.0 Hz), 3.25 (s, 3H), 2.38 (dd, 1H, J=8.0 Hz, J=
14.0 Hz), 2.17 (dd, 1H, J=6.4 Hz, J=14.0 Hz), 1.53 (s,
3H), 1.33 (s, 3H), 0.90 (s, 9H), 0.17 (s, 3H), 0.14 (s, 3H).
13C NMR (100 MHz, CDCl3): d 170.8, 108.6, 99.6, 76.6,
73.5, 73.4, 60.3, 58.0, 52.5, 48.5, 33.0, 28.1, 26.2, 25.9, 25.6,
18.1, À3.7, À5.3. HRMS calcd. for C19H35N3O7Si+Na
468.2142, found 468.2142.
1
The supporting information contains H, 13C and 13C
DEPT NMR spectra of all new compounds.
Acknowledgements
We thank Board of Research in Nuclear Sciences
(BRNS), Sanction No. 37(2)/14/32/2014-BRNS for finan-
cial support.
References
[1] a) Essentials of Glycobiology, 2nd Ed. (Eds.: A. Varki, R. D.
Cummings, J. D. Esko, H. H. Freeze, P. Stanley, C. R. Ber-
tozzi, G. W. Hart, M. E. Etzler), Cold Spring Harbor Labo-
ratory Press, New York, 2009; b) Carbohydrates in Chemis-
try and Biology (Eds.: B. Ernst, G. W. Hart, P. Sinay¨), Wiley,
Weinheim, 2000, Vols. 1–4.
[2] a) U. Westerlind, H. Kunz, Chimia 2011, 65, 30–34; b) A.
Liakatos, H. Kunz, Curr. Opin. Mol. Ther. 2007, 9, 35–44;
c) T. Buskas, P. Thompson, G. J. Boons, Chem. Commun.
2009, 5335–5349; d) L. Morelli, L. Poletti, L. Lay, Eur. J.
Org. Chem. 2011, 5723–5777.
(S)-Methyl 2-azido-3-((3aR,6S,7R,7aR)-7-((tert-butyldi-
methylsilyl)oxy)-2,2-dimethyltetrahydro-3aH-[1,3]dioxo-
lo[4,5-c]pyran-6-yl)propanoate (23): Compound 23 was
synthesized from 18 (100 mg, 0.22 mmol) by following the
procedure described for compound 5. Compound 23
(76 mg, 82%) was obtained as a colorless gum. [a]D25
À29.5 (c 1, CHCl3); IR (neat): nmax 2991, 2958, 2931, 2854,
1
2104, 1747, 1468, 1435, 1380 cmÀ1. H NMR (400 MHz,
CDCl3): d 4.10–4.20 (m, 3H), 3.89 (t, 1H, J=6.4 Hz), 3.75
(s, 3H), 3.63 (dd, 1H, J=2.4 Hz, J=13.6 Hz), 3.40 (dd,
1H, J=6.8 Hz, J=16.4 Hz), 3.08 (dt, 1H, J=2.0 Hz, J=
9.6 Hz), 2.33 (ddd, 1H, J=2.0 Hz, J=7.6 Hz, J=14.0 Hz),
1.83–1.91 (m, 1H), 1.51 (s, 3H), 1.34 (s, 3H), 0.88 (s, 9H),
0.14 (s, 3H), 0.08 (s, 3H). 13C NMR (100 MHz, CDCl3): d
170.6, 109.2, 79.7, 75.5, 74.4, 74.0, 66.3, 58.9, 52.4, 33.9,
29.6, 28.1, 26.3, 25.8, 18.0, À3.9, À5.0. HRMS calcd. for
C18H33N3O6Si+Na, 438.2036 found 438.2035.
[3] a) P. Compain, O. R. Martin, Bioorg. Med. Chem. 2001, 9,
3077–3092; b) P. Brown, D. S. Eggleston, R. C. Haltiwanger,
R. L. Jarvest, L. Mensah, P. J. O’Hanlon, A. J. Pope, Bioorg.
Med. Chem. Lett. 2001, 11, 711–714.
[4] Carbohydrate-based Drug Discovery (Ed. C.-H. Wong),
Wiley-VCH, Weinheim, 2003, Vols. 1–2.
[5] a) C. R. Bertozzi, P. D. Hoeprich Jr., M. D. Bednarski, J.
Org. Chem. 1992, 57, 6092–6094; b) C. Palomo, M. Oiar-
bide, A. Landa, M. C. Gonzꢁlez-Rego, J. M. Garcꢂa, A.
Gonzꢁlez, J. M. Odriozola, M. Martꢂn-Pastor, A. Linden, J.
Am. Chem. Soc. 2002, 124, 8637–8643; c) P. Arya, A. Bark-
ley, K. D. Randell, J. Comb. Chem. 2002, 4, 193–198;
d) S. A. W. Gruner, E. Locardi, E. Lohof, H. Kessler, Chem.
Rev. 2002, 102, 491–514; e) A. Dondoni, A. Marra, Chem.
Rev. 2000, 100, 4395–4421; f) R. Hamzavi, C. Meyer, N.
Metzler-Nolte, Org. Biomol. Chem. 2006, 4, 3648–3651.
[6] a) H. Kessler, V. Wittmann, M. Kçck, M. Kottenhahn,
Angew. Chem. Int. Ed. Engl. 1992, 31, 902–904; b) J. R.
Axon, A. L. J. Beckwith, J. Chem. Soc. Chem. Commun.
1995, 549–550; c) J. D. Parrish, R. D. Little, Org. Lett. 2002,
4, 1439–1442.
(S)-Methyl
2-((tert-butoxycarbonyl)amino)-3-
((3aR,6S,7R,7aR)-7-((tert-butyldimethylsilyl)oxy)-2,2-di-
methyltetrahydro-3aH-[1,3]dioxolo[4,5-c]pyran-6-yl)pro-
panoate (24): To a stirred solution of azido carboxylated
sugar 23 (20 mg, 0.048 mmol) in methanol (3 mL), Boc2O
(57 mL, 0.24 mmol) and 10% Pd/C (5 mg) was added. The
reaction mixture was degassed and stirred under hydro-
gen atmosphere for 2 h. After completion of the reaction,
the catalyst was removed by filtration and the filtrate was
concentrated. Purification of the obtained crude product
using silica-gel column chromatography afforded the
compound 24 (21 mg, 89%) as a colorless gum. [a]2D5 À1.4
(c 1, CHCl3); IR (neat): nmax 2926, 2860, 1720, 1490, 1441,
[7] A. Nuzzi, A. Massi, A. Dondoni, Org. Lett. 2008, 10, 4485–
4488.
[8] S. P. Vincent, A. Schleyer, C.-H. Wong, J. Org. Chem. 2000,
65, 4440–4443.
1
1364, 1260, 1216, 1167, 1090 cmÀ1. H NMR (400 MHz,
Isr. J. Chem. 0000, 00, 1 – 9
ꢀ 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.ijc.wiley-vch.de
&7
&
ÞÞ
These are not the final page numbers!

Full Paper
[9] E. G. Nolen, A. J. Kurish, J. M. Potter, L. A. Donahue,
[16] Y. Tao, N. Ding, S. Ren, Y. Li, Tetrahedron. Lett. 2013, 54,
6101–6104.
M. D. Orlando, Org. Lett. 2005, 7, 3383–3386.
[17] a) C. Brand, G. Rauch, M. Zanoni, B. Dittrich, D. B. Werz,
J. Org. Chem. 2009, 74, 8779–8786; b) B. Ramakrishna,
P. R. Sridhar, RSC Adv. 2015, 5, 8142–8145.
[18] The configuration at the anomeric center for 3a, 3b, 4a, and
4b was assigned based on NOE experiments. The stereo-
chemistry a to the ester was assigned based on the synthe-
sized known b-C-galactosyl azido esters 5 and 6.
[19] B. Ramakrishna, P. R. Sridhar, Org. Lett. 2013, 15, 4474–
4477.
[20] CCDC deposition no: 1434490. Crystal data for 16
(C18H32O6Si): Mr =372.53, orthorhombic, space group P21,
a=10.1107 ꢄ, b=12.5871 ꢄ, c=16.6445 ꢄ, b=90 (10)8, V=
2118.25(19) ꢄ3 , Z=4, Mo Ka radiation (l=0.71073 ꢄ),
T=298 K; R=0.0422(3769), wR2=0.0987(4591).
[10] T. Vidal, A. Haudrechy, Y. Langlois, Tetrahedron Lett. 1999,
40, 5677–5680.
[11] M. K. Gurjar, A. S. Mainkar, M. Syamala, Tetrahedron:
Asymmetry 1993, 4, 2343–2346.
[12] V. N. Thota, J. Gervay-Hague, S. S. Kulkarni, Org. Biomol.
Chem. 2012, 10, 8132–8139.
[13] A. Lieberknecht, H. Griesser, B. Krꢃmer, R. D. Bravo, P. A.
Colinas, R. J. Grigera, Tetrahedron 1999, 55, 6475–6482.
[14] For reviews on DA cyclopropanes please see: a) H.-U. Reis-
sig, R. Zimmer, Chem. Rev. 2003, 103, 1151–1196; b) M.
Yu, B. L. Pagenkopf, Tetrahedron 2005, 61, 321–347;
c) C. A. Carson, M. A. Kerr, Chem. Soc. Rev. 2009, 38,
3051–3060; d) T. F. Schneider, J. Kaschel, D. B. Werz,
Angew. Chem. Int. Ed. 2014, 53, 5504–5523; e) M. A.
Cavitt, L. H. Phun, S. France, Chem. Soc. Rev. 2014, 43,
804–818.
[21] The stereochemistry a to the ester is tentatively assigned
based on the proposed mechanism.
[15] a) P. R. Sridhar, K. C. Ashalu, S. Chandrasekaran, Org. Lett.
2004, 6, 1777–1779; b) P. R. Sridhar, P. V. Kumar, K. Sesha-
dri, R. Satyavati, Chem. Eur. J. 2009, 15, 7526–7529.
Received: November 9, 2015
Accepted: December 8, 2015
Published online: && &&, 0000
Isr. J. Chem. 0000, 00, 1 – 9
ꢀ 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.ijc.wiley-vch.de
&8
&
ÞÞ
These are not the final page numbers!

Full Paper
FULL PAPERS
B. Ramakrishna, C. Sudharani,
P. R. Sridhar*
&& – &&
Synthesis of b-C-Glycosyl Amino
Acids by Ring Opening of Donor-
Acceptor Spiro-
cyclopropanecarboxylated Sugars
Isr. J. Chem. 0000, 00, 1 – 9
ꢀ 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.ijc.wiley-vch.de
&9
&
ÞÞ
These are not the final page numbers!